In the preparation of a suspension, emulsion or solution from a mixture of starting materials, it is a known technique to mix the starting materials in a tank and continuously circulate a portion of the resulting mixture through an external homogenizing or emulsifying unit. The external homogenizing unit is typically designed so that a small portion of the reaction mixture is continuously withdrawn from the bottom of the tank and is returned above it to the tank. Thus, the incompletely homogenized starting materials that may be present at the bottom of the tank are withdrawn therefrom, passed through the external homogenizing or emulsifying unit and then returned to the tank.
Colloid mills are typically employed as external homogenizing or emulsifying units, although a wide variety of other mixers and grinders have also been employed for this purpose. Colloid mills break up agglomerates of solid particles or subdivide droplets of a dispersed liquid, by means of high speed fluid shear. A typical colloid mill employs a rotor which rotates rapidly within and close to the surface of a stator. The materials to be formed into a fine dispersion are fed between the rotor and the stator and thereby are subjected to intense shear and centrifugal force whereby the dispersion is formed. Colloid mills are complex in structure and they are not easy to sterilize. Moreover, they generate a considerable amount of heat during operation, which makes it troublesome to use them to form compositions containing heat-sensitive materials.
Concerning mixers generally, a wide variety of mixers with various mixer head designs are known and are in common use. One known type of mixer employs, as a mixing head, a rotatable tubular member having radial slots in the side wall thereof. The fluid to be homogenized is drawn axially into the interior of the rotating tubular head and then is expelled radially outwardly through the slots by centrifugal force, whereby the starting materials are intensively mixed. Fins or blades are often disposed within the tubular mixer head to enhance the mixing action.
Commonly a mixer head is disposed inside a casing and is rotated by a drive shaft which is driven by a motor located outside of the casing. In such a construction, it is necessary to provide a mechanical seal around the drive shaft to prevent leakage of the material being mixed. A wide variety of mechanical seals, including seals having various configurations of O-rings and sealing rings, have been employed. However, it has been difficult to obtain, at reasonable cost, an effective mechanical seal for use with rotatable, high speed, tubular mixer heads.
In the preparation of pharmaceutical suspensions and emulsions, it is important to minimize and, if possible, eliminate foaming within the main mixing tank of the apparatus. When vigorous agitation is employed within the main mixing tank, vortex formation occurs and an excessive amount of foam can be produced. In the preparation of pharmaceutical suspensions and emulsions, it has been difficult to achieve intensive mixing of the starting materials without simultaneously causing excessive foaming in the main mixing tank.
A further problem with devices for the preparation of pharmaceutical suspensions and emulsions stems from the need periodically to sterilize the entire interior of the apparatus. It is preferred to sterilize a mixing apparatus by exposing it to steam under pressure for a suitable period of time. If the mixing apparatus, however, is of complex internal structure, it may not be possible to readily sterilize it, as is, by steam under pressure. Thus, additional time and expense will be required to sterilize such a complex mixing apparatus, which is undesirable.
Accordingly, it is an object of the present invention to provide a mixing apparatus for forming a suspension, emulsion or solution, which apparatus is capable of producing a very homogenous product without causing excessive foaming in the main mixing tank.
It is a further object of the invention to provide a mixing apparatus, as aforesaid, which is particularly adapted for preparing pharmaceutical solutions, emulsions and suspensions and which apparatus can be easily cleaned and sterilized, preferably with pressurized live steam.
An additional object of the invention is to provide a mixing apparatus, as aforesaid, in which a mixture of materials to be formed into a suspension, emulsion or solution is withdrawn from the bottom of a main mixing tank and is flowed through an external recirculation loop wherein the mixture is subjected to high shear forces effective to form the withdrawn materials into the desired suspension, emulsion or solution, and then the suspension, emulsion or solution is returned to the main tank.
A further object of the invention is to provide a mixing apparatus for the preparation of suspensions, emulsions and solutions, as aforesaid, which includes an improved shaft seal for preventing leakage of the solution, emulsion or suspension around the drive shaft used to rotate the mixer head.
Other objects and advantages of the present invention will be apparent from the following specification, taken in conjunction with the accompanying drawings.